JAK inhibitor therapy in a child with inherited usp18 deficiency

Fahad Alsohime, Marta Martin-Fernandez, Mohamad Hani Temsah, Majed Alabdulhafid, Tom Le Voyer, Malak Alghamdi, Xueer Qiu, Najla Alotaibi, Areej Alkahtani, Sofija Buta, Emmanuelle Jouanguy, Ayman Al-Eyadhy, Conor Gruber, Gamal M. Hasan, Fahad A. Bashiri, Rabih Halwani, Hamdy H. Hassan, Saleh Al-Muhsen, Nouf Alkhamis, Zobaida AlsumJean Laurent Casanova, Jacinta Bustamante, Dusan Bogunovic, Abdullah A. Alangari

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery.

Original languageEnglish
Pages (from-to)256-265
Number of pages10
JournalNew England Journal of Medicine
Issue number3
StatePublished - 16 Jan 2020


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